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Int. J. Mol. Sci. 2013, 14(7), 14321-14332; doi:10.3390/ijms140714321

Thrombospondin-1 Is a Putative Target Gene of Runx2 and Runx3

1 Institute of Genetics and Cell Biology, Northeast Normal University, Changchun 130024, China 2 Division of Surgery, Indian Veterinary Research Institute, Izatnagar 243122, India 3 School of Dentistry, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan 4 Key Laboratory of Molecular Epigenetics of Ministry of Education of China, Northeast Normal University, Changchun 130024, China These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 22 May 2013 / Accepted: 26 June 2013 / Published: 10 July 2013
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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Thrombospondin-1 (TSP-1), a matricellular protein widely acclaimed to be involved in the inhibition of angiogenesis and tumorigenesis, is synthesized and secreted by many cell types, including osteoblast and cancer cells. TSP-1 is highly upregulated during early stage of osteogenesis, whereas it inhibits terminal osteoblast differentiation. Expression of TSP-1 is downregulated in cancer cells, and its ectopic expression has been shown to restrain tumor growth. Transcriptional regulation of TSP-1 in osteogenesis and cancer is poorly understood; this prompted us to study its regulation by the two key regulators of the aforementioned processes: Runx2 and Runx3. Through a PCR-based cDNA subtraction technique, we identified and cloned a cDNA fragment for mouse TSP-1, whose expression was dramatically upregulated in response to Runx2 expression in mesenchymal stem cells. Moreover, TSP-1 expression was considerably reduced in the lung of Runx2 knockout mouse. On the other hand, TSP-1 gene expression drastically increased at both the transcriptional and translational levels in response to Runx3 expression in B16-F10 melanoma cells. In line with this, Runx2 and Runx3 bound to the TSP-1 promoter and stimulated its activity. Hence, these results provide first line of evidence that TSP-1 is a transcriptional target gene of Runx2 and Runx3.
Keywords: TSP-1; Runx2; Runx3; C3H10T1/2 stem cells; osteoblast; metastasis; cancer; melanoma; B16-F10; angiogenesis TSP-1; Runx2; Runx3; C3H10T1/2 stem cells; osteoblast; metastasis; cancer; melanoma; B16-F10; angiogenesis
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Shi, X.; Deepak, V.; Wang, L.; Ba, X.; Komori, T.; Zeng, X.; Liu, W. Thrombospondin-1 Is a Putative Target Gene of Runx2 and Runx3. Int. J. Mol. Sci. 2013, 14, 14321-14332.

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